""
Nolvadex vs
Clomid"
by William Llewellyn
I have received a lot of heat lately about my preference for
Nolvadex over
Clomid, which I hold for all purposes of use (in the bodybuilding world anyway); as an anti-estrogen, an HDL (good) cholesterol-supporting drug, and as a
testosterone-stimulating compound. Most people use
Nolvadex to combat gynecomastia over
Clomid anyway, so that is an easy sell. And for cholesterol, well, most bodybuilders unfortunately pay little attention to this important issue, so by way of disinterest, another easy opinion to discuss. But when it comes to using
Nolvadex for increasing endogenous
testosterone release, bodybuilders just do not want to hear it. They only seem to want
Clomid. I can only guess that this is based on a long rooted misunderstanding of the actions of the two drugs. In this article I would therefore like to discuss the specifics for these two agents, and explain clearly the usefulness of
Nolvadex for the specific purpose of increasing
testosterone production.
Clomid and
Nolvadex
I am not sure how
Clomid and
Nolvadex became so separated in the minds of bodybuilders. They certainly should not be.
Clomid and
Nolvadex are both anti-estrogens belonging to the same group of triphenylethylene compounds. They are structurally related and specifically classified as selective estrogen receptor modulators (SERMs) with mixed agonistic and antagonistic properties. This means that in certain tissues they can block the effects of estrogen, by altering the binding capacity of the receptor, while in others they can act as actual estrogens, activating the receptor. In men, both of these drugs act as anti-estrogens in their capacity to oppose the negative feedback of estrogens on the hypothalamus and stimulate the heightened release of GnRH (Gonadotropin Releasing Hormone). lh - leutenizing hormone - output by the pituitary will be increased as a result, which in turn can increase the level of
testosterone by the testes. Both drugs do this, but for some reason bodybuilders persist in thinking that
Clomid is the only drug good at stimulating
testosterone. What you will find with a little investigation however is that not only is
Nolvadex useful for the same purpose, it should actually be the preferred agent of the two.
Pituitary Sensitivity to GnRH
Studies conducted in the late 1970's at the University of Ghent in Belgium make clear the advantages of using
Nolvadex instead of
Clomid for increasing
testosterone levels (1). Here, researchers looked the effects of
Nolvadex and
Clomid on the endocrine profiles of normal men, as well as those suffering from low sperm counts (oligospermia). For our purposes, the results of these drugs on hormonally normal men are obviously the most relevant. What was found, just in the early parts of the study, was quite enlightening.
Nolvadex, used for 10 days at a dosage of 20mg daily, increased serum
testosterone levels to 142% of baseline, which was on par with the effect of 150mg of
Clomid daily for the same duration (the
testosterone increase was slightly, but not significantly, better for
Clomid). We must remember though that this is the effect of three 50mg tablets of
Clomid. With the price of both a 50mg
Clomid and 20mg
Nolvadex typically very similar, we are already seeing a cost vs. results discrepancy forming that strongly favors the
Nolvadex side.
But something more interesting is happening. Researchers were also conducting GnRH stimulation tests before and after various points of treatment with
Nolvadex and
Clomid, and the two drugs had markedly different results. These tests involved infusing patients with 100mcg of GnRH and measuring the output of pituitary lh - leutenizing hormone - in response. The focus of this test is to see how sensitive the pituitary is to Gonadotropin Releasing Hormone. The more sensitive the pituitary, the more lh - leutenizing hormone - will be released. The tests showed that after ten days of treatment with
Nolvadex, pituitary sensitivity to GnRH increased slightly compared to pre-treated values. This is contrast to 10 days of treatment with 150mg
Clomid, which was shown to consistently DECREASE pituitary sensitivity to GnRH (more lh - leutenizing hormone - was released before treatment). As the study with
Nolvadex progresses to 6 weeks, pituitary sensitivity to GnRH was significantly higher than pre-treated or 10-day levels. At this point the same 20mg dosage was also raising
testosterone and lh - leutenizing hormone - levels to an average of 183% and 172% of base values, respectively, which again is measurably higher than what was noted 10 days into therapy. Within 10 days of treatment
Clomid is already exerting an effect that is causing the pituitary to become slightly desensitized to GnRH, while prolonged use of
Nolvadex serves only to increase pituitary sensitivity to this hormone. That is not to say
Clomid won't increase
testosterone if taken for the same 6 week time period. Quite the opposite is true. But we are, however, noticing an advantage in
Nolvadex.
The Estrogen
Clomid
The above discrepancies are likely explained by differences in the estrogenic nature of the two compounds. The researchers' clearly support this theory when commenting in their paper, "The difference in response might be attributable to the weak intrinsic estrogenic effect of
Clomid, which in this study manifested itself by an increase in transcortin and
testosterone/estradiol-binding globulin [sex hormone binding globulin ] levels; this increase was not observed after
Tamoxifen treatment". In reviewing other theories later in the paper, such as interference by increased androgen or estrogen levels, they persist in noting that increases in these hormones were similar with both drug treatments, and state that," ?a role of the intrinsic estrogenic activity of
Clomid which is practically absent in
Tamoxifen seems the most probable explanation".
Although these two are related anti-estrogens, they appear to act very differently at different sites of action.
Nolvadex seems to be strongly anti-estrogenic at both the hypothalamus and pituitary, which is in contrast to
Clomid, which although a strong anti-estrogen at the hypothalamus, seems to exhibit weak estrogenic activity at the pituitary. To find further support for this we can look at an in-vitro animal study published in the American Journal of Physiology in February 1981 (2). This paper looks at the effects of
Clomid and
Nolvadex on the GnRH stimulated release of lh - leutenizing hormone - from cultured rat pituitary cells. In this paper, it was noted that incubating cells with
Clomid had a direct estrogenic effect on cultured pituitary cell sensitivity, exerting a weaker but still significant effect compared to estradiol.
Nolvadex on the other hand did not have any significant effect on lh - leutenizing hormone - response. Furthermore it mildly blocked the effects of estrogen when both were incubated in the same culture.
Conclusion
To summarize the above research succinctly,
Nolvadex is the more purely anti-estrogenic of the two drugs, at least where the hpta - hypothalamic-pituitary-testicular axis - (Hypothalamic-Pituitary-Testicular Axis) is concerned. This fact enables
Nolvadex to offer the male bodybuilder certain advantages over
Clomid. This is especially true at times when we are looking to restore a balanced hpta - hypothalamic-pituitary-testicular axis - , and would not want to desensitize the pituitary to GnRH. This could perhaps slow recovery to some extent, as the pituitary would require higher amounts of hypothalamic GnRH in the presence of
Clomid in order to get the same level of lh - leutenizing hormone - stimulation.
Nolvadex also seems preferred from long-term use, for those who find anti-estrogens effective enough at raising
testosterone levels to warrant using as anabolics. Here
Nolvadex would seem to provide a better and more stable increase in
testosterone levels, and likely will offer a similar or greater effect than
Clomid for considerably less money. The potential rise in sex hormone binding globulin levels with
Clomid, supported by other research (3), is also cause for concern, as this might work to allow for comparably less free active
testosterone compared to
Nolvadex as well. Ultimately both drugs are effective anti-estrogens for the prevention of gynecomastia and elevation of endogenous
testosterone."
